The first two principal IL-1 receptor co-expression remodeling in allergic and autoimmune inflammation reveals disease-associated differences
Abstract
IntroductionInterleukin-1 is a central mediator of inflammation, with its activity governed by the opposing functions of the signaling-competent receptor IL-1R1 and the inhibitory decoy receptor IL-1R2. However, comprehensive profiling of IL-1 receptor co-expression across immune cell subsets in diseases with distinct pathogenesis remains limited.MethodsWe investigated the expression and co-expression patterns of IL-1R1 and IL-1R2 on twelve peripheral blood immune cell populations from patients with rheumatoid arthritis, patients with bronchial asthma, and healthy donors using multicolor flow cytometry. Receptor density was quantified as antibody-binding capacity per cell. Unsupervised clustering and logistic regression were applied to identify disease-associated candidate signatures and to develop exploratory diagnostic algorithms.ResultsExploratory dimensionality reduction suggested separation of the three groups in this cohort, with each disease displaying a distinct IL-1 receptor remodeling pattern. Bronchial asthma was characterized by a global shift toward the double-negative phenotype across most populations, profound decoy receptor deficiency, and a striking predominance of the double-positive phenotype in naive T cells. Rheumatoid arthritis exhibited a less pronounced double-negative shift, selective loss of decoy receptor on monocytes, and mixed cytotoxic T cell profiles with preserved signaling-competent phenotypes. Logistic regression models incorporating three parameters for RA showed high discrimination in this case-control cohort, with apparent and cross-validated performance remaining robust for this disease.ConclusionThese findings indicate that allergic and autoimmune inflammation are associated with distinct, cell-subset-specific IL-1 receptor signatures consistent with their divergent immunopathogenesis. The identified receptor profiles may serve as candidate biomarkers and provide hypotheses for mechanistic studies of interleukin-1 pathway dysregulation in chronic inflammatory diseases. The model requires external validation before any clinical application.
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BibTeX
@article{zhukova2026first,
title = {{The first two principal IL-1 receptor co-expression remodeling in allergic and autoimmune inflammation reveals disease-associated differences}},
author = {J. V. Zhukova and J. A. Lopatnikova and N. S. Shkaruba and A. E. Sizikov and V. M. Nepomniashchikch and D. V. Demina and S. V. Sennikov},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1988144},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1988144},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The first two principal IL-1 receptor co-expression remodeling in allergic and autoimmune inflammation reveals disease-associated differences
AU - J. V. Zhukova
AU - J. A. Lopatnikova
AU - N. S. Shkaruba
AU - A. E. Sizikov
AU - V. M. Nepomniashchikch
AU - D. V. Demina
AU - S. V. Sennikov
PY - 2026
DA - 2026/11/10
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1988144
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1988144
AB - IntroductionInterleukin-1 is a central mediator of inflammation, with its activity governed by the opposing functions of the signaling-competent receptor IL-1R1 and the inhibitory decoy receptor IL-1R2. However, comprehensive profiling of IL-1 receptor co-expression across immune cell subsets in diseases with distinct pathogenesis remains limited.MethodsWe investigated the expression and co-expression patterns of IL-1R1 and IL-1R2 on twelve peripheral blood immune cell populations from patients with rheumatoid arthritis, patients with bronchial asthma, and healthy donors using multicolor flow cytometry. Receptor density was quantified as antibody-binding capacity per cell. Unsupervised clustering and logistic regression were applied to identify disease-associated candidate signatures and to develop exploratory diagnostic algorithms.ResultsExploratory dimensionality reduction suggested separation of the three groups in this cohort, with each disease displaying a distinct IL-1 receptor remodeling pattern. Bronchial asthma was characterized by a global shift toward the double-negative phenotype across most populations, profound decoy receptor deficiency, and a striking predominance of the double-positive phenotype in naive T cells. Rheumatoid arthritis exhibited a less pronounced double-negative shift, selective loss of decoy receptor on monocytes, and mixed cytotoxic T cell profiles with preserved signaling-competent phenotypes. Logistic regression models incorporating three parameters for RA showed high discrimination in this case-control cohort, with apparent and cross-validated performance remaining robust for this disease.ConclusionThese findings indicate that allergic and autoimmune inflammation are associated with distinct, cell-subset-specific IL-1 receptor signatures consistent with their divergent immunopathogenesis. The identified receptor profiles may serve as candidate biomarkers and provide hypotheses for mechanistic studies of interleukin-1 pathway dysregulation in chronic inflammatory diseases. The model requires external validation before any clinical application.
SN - 1664-3224
ER -